The purpose of this investigation is to understand the regulation of the metabolism in the pathogenic leishmania and Trypanosoma cruzi. In addition, it will contrast purine metabolism in the culture forms and extracellular forms of these organisms. The extracellular forms are grown in vitro; the intracellular forms of the leishmania are grown in P388Dl macrophage cell culture and those of T. cruzi are grown in L929 fibroblasts. Purine metabolism will be studied using radiolabeled purine bases to evaluate the activity of salvage pathways in these organisms; analysis generally will be by high performance liquid chromatography and liquid scintillation counting. In addition to these investigations, we will use pyrazolopyrimidines, of proven antileishmanial and antitrypanosomal effectiveness, as biochemical probes to investigate purine metabolism in these organisms per se and also will study pyrazolopyrimidine metabolism specifically to evaluate its future role in chemotherapy of leishmaniasis and trypanosomiasis.